The overall goal of this proposal is to characterize and to optimize a new animal model utilizing a chimeric SIVmac/HIV-1 virus. The chimeric virus contains the long terminal repeats and intact gag, pro, pol, vif, vpx, vpr and nef genes of an infectious, pathogenic clone of SIVmac239 and the tat, rev, vpu and env genes of HIV-1. This chimeric virus, unlike HIV-1, replicates in macaque peripheral blood mononuclear cells and in cynomolgus monkeys. This virus should be useful for HIV-1 vaccine development. This revised study will focus on two specific aims: 1) To optimize the chimeric virus for persistence and pathogenicity in monkeys by in vivo passage as well as vpu and env gene modifications; and 2) to characterize the antiviral immune response.